The pathogenesis of retroviral induced leukemia and immunological methods for the prevention of this form of leukemia will be investigated in AKR mice. Preliminary results have demonstrated that an idiotypic network exists in preleukemic AKR mice. The anti-(antiviral) antibodies, or anti- idiotypes, found in these mice bind to leukemia cells and may bind to viral receptors on these cells. Moreover, the anti-idiotypes induce AKR T-cell proliferation in culture. Immunization of mice with anti-idiotype results in antibodies directed against retrovirus. These preliminary observations will be extended in the present project. The first aspect of the project will be to isolate the viral receptor on the cell surface by taking advantage of the binding of anti-idiotypic antibodies to cells. The receptor will be immunoprecipitated from labelled leukemia cell lysates and analyzed by SDS-PAGE. Partial amino acid sequences will determined and compared with known membrane components. The anti-idiotypic antibody will be used to screen a DNA library obtained from receptor-bearing cells in order to clone the gene for the receptor protein. The second part of the project will be to investigate the characteristics of receptor bearing T cells. This will be accomplished by establishing a T cell line which proliferates in response to anti-idiotypic antibody, and determining its susceptibility to viral infection and transformation. The last part of the study will be to immunize mice with anti-idiotypic antibody in order to generate an anti- retroviral response. Such immunizations will be used in protection experiments using several models of induced leukemia.